MicroRNAs (miRNAs ) are small non-coding RNAs
that regulate gene expression. We hypothesised that the functions
of certain miRNAs and changes to their patterns of expression may
be crucial in the pathogenesis of nonunion. Healing fractures and
atrophic nonunions produced by periosteal cauterisation were created
in the femora of 94 rats, with 1:1 group allocation. At post-fracture
days three, seven, ten, 14, 21 and 28, miRNAs were extracted from
the newly generated tissue at the fracture site. Microarray and
real-time polymerase chain reaction (PCR) analyses of day 14 samples
revealed that five miRNAs, miR-31a-3p, miR-31a-5p, miR-146a-5p,
miR-146b-5p and miR-223-3p, were highly upregulated in nonunion.
Real-time PCR analysis further revealed that, in nonunion, the expression
levels of all five of these miRNAs peaked on day 14 and declined
thereafter. Our results suggest that miR-31a-3p, miR-31a-5p, miR-146a-5p,
miR-146b-5p and miR-223-3p may play an important role in the development
of nonunion. These findings add to the understanding of the molecular mechanism
for nonunion formation and may lead to the development of novel
therapeutic strategies for its treatment. Cite this article:
It is well known that blood flow is a critical key component of fracture repair. Previously, we demonstrated that transcutaneous application of CO2 increased blood flow in the human body. To date, there has been no report investigating the effect of the carbonated therapy on fracture repair. We hypothesized that the transcutaneous application of CO2 to fracture site would accelerate fracture repair.Introduction
Hypothesis
In most cases of stable type medial femoral neck fracture and some cases of dislocated medial femoral neck fracture, internal fixation was undertaken. Dual SC Screw (DSCS) System is an internal fixation device which has sliding mechanism and preventing mechanism of back out of the screw. The purpose of this study is to evaluate the results and complication of medial femoral neck fracture treated with DSCS. Fifty two patients operated for fractures of the medial femoral neck with DSCS were identified as the study population. All patients followed up at least 2years. Outcome measures included the period of bone union, revision surgery, operating times and clinical symptoms and complication.Introduction
Methods
Recently, some case reports have been published, in which nonunions were successfully healed with parathyroid hormone 1–34 (PTH) administration. Previously, we demonstrated that the intervening tissue at the nonunion site contains multilineage mesenchymal progenitor cells and plays an important role during the healing process of nonunion. We investigated the effect of PTH on osteogenic differentiation of human nonunion tissue-derived cells (NCs) in vitro. We hypothesized that PTH directly promoted osteogenic differentiation of NCs.Introduction
Hypothesis
Failures in fracture healing are mainly caused by a lack of neovascularization. We have previously demonstrated that G-CSF-mobilized peripheral blood (GM-PB) CD34+ cells, an endothelial progenitor enriched cell population, contributed to fracture healing via vasculogenesis and osteogenesis. We postulated the hypothesis that local transplantation of culture expanded bone marrow (cEx-BM) CD34+ cells could exhibit therapeutic potential for fracture healing. BM CD34+ cells were cultured in specific medium with 5 growth factors for 1week. A reproducible model of femoral fracture was created in nude rats with periosteum cauterization, which leads to nonunion at 8 weeks post-fracture. Rats received local administration of the following cells or PBS alone(1)cEx-BM, (2)BM, (3)GM-PB CD34+ cells or (4)PBS.Introduction
Materials
Low-intensity pulsed ultrasound (LIPUS) has been reported to enhance healing of fracture and nonunion. Bone morphogenetic protein-7 (BMP-7) has also been reported to promote bone formation. Recently, we demonstrated progenitor cells with osteogenic/chondrogenic differentiation potential existed in human fracture hematoma and nonunion tissue. We hypothesised the combined application of LIPUS and BMP-7 would cause major effect on osteogenesis of hematoma-derived cells (HCs) and nonunion tissue-derived cells (NCs).Introduction
Hypothesis
The hematoma occurring at a fracture site is known to play an important role in fracture healing. Previously, we demonstrated that fracture hematoma contained multilineage mesenchymal progenitor cells. On the other hand, the process of fracture healing is associated by two different mechanisms, intramembranous and endochondral. However, there are no reports proving the details about cellular analysis in the process of endochondoral ossification. We hypothesized that one of the cell origins for endochondral ossification after fracture was hematoma.Introduction
Hypothesis
Plate fixations have been recommended for dislocated clavicle fractures. However, existing plates are inadequate for morphological compatibility with the clavicle. The aim of this study is to measure the anatomical shape of the clavicle and to compare the radiographical and clinical outcomes of our tree-dimensional (3D) reconstruction plate with conventional straight plate. Chest CT image of 15 patients with normal clavicle were analyzed. Their clavicles were reconstructed and measured their anatomical variables. A hospital-based case-control study was conducted, including a consecutive series of 52 patients with displaced midshaft clavicle fractures. 3D reconstruction plate was used for 26 patients and another 26 patients were treated with conventional straight plate. Outcome measures included the period of bone union, revision surgery, operating times and clinical symptoms using DASH score.Introduction
Methods
Our previous study using microarray analysis showed that Rad (Ras associated with diabetes) was highly expressed in nonunion. The purpose of this study is to investigate the gene expression and immunolocalization of Rad, and other Ras-related G proteins: Rem1 and Rem2 in fracture/nonunion site using rat experimental models. We hypothesized that Rad had a significant role in nonunion formation.Introduction
Hypothesis
CXC chemokine receptor 4 (CXCR4) is a specific receptor for stromal-derived-factor 1 (SDF-1). SDF-1/CXCR4 interaction contributes to the regulation of endotherial progenitor cell (EPC) recruitment in ischemic tissues. The purpose of this study is to investigate the mechanistic function of CXCR4 on EPCs for bone fracture healing. We made CXCR4 gene knockout mice using the Cre/loxP system. A reproducible model of femoral fracture was created in both Tie2-Cre CXCR4 knockout mice (CXCR4KO) and wild type mice (control). To evaluate gain function of the SDF-1/CXCR4 pathway, we set three groups of the SDF-1 intraperitoneally injected group, wild type group, and SDF-1 injected CXCR4 KO group.Introduction
Materials and methods
iPSCs represent a promising cell source for bone regeneration. To generate osteoprogenitor cells, most protocols use the generation of embryoid bodies (EBs). However, these protocols give rise to heterogeneous population of different cell lineage. We hypothesized that a direct plating method without EB formation step could be an efficient protocol for generating a homogeneous population of osteoprogenitor cells from iPSCs.Introduction
Hypothesis
Parathyroid hormone 1–34 (PTH) has been reported to accelerate fracture healing. Previously, we demonstrated human fracture hematoma contained osteo-/chondro-progenitor cells. To date, there has been no study investigating the effect of PTH on fracture hematoma-derived cells (HCs) in vitro. We hypothesized PTH treatment affected osteogenesis and chondrogenesis of HCs.Introduction
Hypothesis
Many surgeons assess biological activity of fracture nonunion by the presence or absence of callus using radiograph. However, it is difficult to assess biological activity only by radiographic appearance. Bone scintigraphy reflects blood supply and bone metabolism and is possibly useful to assess biological activity in nonunion cases. We hypothesized that poor callus visualization did not always mean lack of biological activity.Introduction
Hypothesis
The therapeutic potential of hematopoietic stem cells for fracture healing has been demonstrated with mechanistic insight of vasculogenesis and osteogenesis enhancement. Lnk has recently been proved an essential inhibitory signaling molecule in SCF-c-Kit signaling pathway for stem cell self-renewal demonstrating enhanced hematopoietic and osteogenic reconstitution in Lnk-deficient mice. We investigated the hypothesis that down regulation of Lnk enhances regenerative response via vasculogenesis and osteogenesis in fracture healing. A reproducible model of femoral fracture was created in mice. Immediately after fracture creation, mice received local administration of the following materials with AteloGene, 10μM (1)Lnk siRNA, (2)control siRNA.Introduction
Methods
